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February 27, 2013
Not What It Says On the Label, Though
The topic of compound purity has come up here before, as well it should. Every experienced medicinal chemist knows that when you have an interesting new hit compound, that one of the first things to do is go back and make sure that it really is what it says on the label. Re-order it from the archive (in both powder and DMSO stock), re-order it if it's from a commercial source, and run it through the LC/MS and the NMR. (And as one of those links above says, if you have any thought that metal reagents were used to make the compound, check for those, too - they can be transparent to LC and NMR).
So when you do this, how many compounds flunk? Here are some interesting statistics from the folks at Emerald:
Recently, we selected a random set of commercial fragment compounds for analysis, and closely examined those that failed to better understand the reasons behind it. The most common reason for QC failure was insolubility (47%), followed by degradation or impurities (39%), and then spectral mismatch (17%) [Note: Compounds can acquire multiple QC designations, hence total incidences > 100% ]. Less than 4% of all compounds assayed failed due to solvent peak overlap or lack of non-exchangeable protons, both requirements for NMR screening. Failure rates were as high as 33% per individual vendor, with an overall average of 16%. . .
I very much wish that they'd identified that 33% failure rate vendor. But overall, they're suggesting that of 10 to 15% compounds will wipe out, regardless of source. Now, you may not feel that solubility is a key criterion for your work, because you're not doing NMR assays. (That's one that will only get worse as you move out of fragment-sized space, too). But that "degradation or impurities" category is still pretty significant. What are your estimates for commercial-crap-in-a-vial rates?
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